Gefitinib, Paclitaxel, and Radiation Therapy in Treating Patients With Advanced or Recurrent Squamous Cell Carcinoma of the Head and Neck

NCT00083057 | Completed Phase 1

• 3 other identifiers: 04014104-C-0141CDR0000362055
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

RATIONALE: Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving gefitinib and paclitaxel together with radiation therapy may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of gefitinib and paclitaxel when given together with radiation therapy in treating patients with advanced or recurrent squamous cell carcinoma (cancer) of the head and neck.

Conditions

Head and Neck Cancer

Keywords

stage III squamous cell carcinoma of the lip and oral cavity; stage IV squamous cell carcinoma of the lip and oral cavity; recurrent squamous cell carcinoma of the lip and oral cavity; stage III squamous cell carcinoma of the hypopharynx; stage IV squamous cell carcinoma of the hypopharynx; recurrent squamous cell carcinoma of the hypopharynx; stage III squamous cell carcinoma of the oropharynx; stage IV squamous cell carcinoma of the oropharynx; recurrent squamous cell carcinoma of the oropharynx; recurrent squamous cell carcinoma of the nasopharynx; stage III squamous cell carcinoma of the nasopharynx; stage IV squamous cell carcinoma of the nasopharynx; recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity; recurrent squamous cell carcinoma of the larynx; stage III squamous cell carcinoma of the larynx; stage IV squamous cell carcinoma of the larynx

Outcome Measures

Primary Outcomes (1)

• Dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) as assessed by CTC v. 3.0

Secondary Outcomes (2)

• Molecular targets analysis of epidermal growth factor receptor (EGFR) downstream signaling pathway as assessed by tissue biopsies and serum cytokines at baseline, days 8 and 29, and 12 weeks after completion of study treatment

• Efficacy as assessed by imagining, histologically, and clinically at 3 months after completion of study treatment and annually for 5 years

Interventions

gefitinib DRUG

paclitaxel DRUG

radiation therapy RADIATION

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed squamous cell (epidermoid) carcinoma of the oral cavity, oropharynx, hypopharynx, larynx, nasopharynx, or maxillary sinus * Stage III or IV disease * Distant metastases allowed provided both of the following are true: * Metastases are confined to the head and neck region * Metastases are encompassable in a radiotherapy field with curative intent * Locally recurrent disease after primary surgery allowed * Meets 1 of the following criteria: * Unresectable disease * Patient prefers chemoradiotherapy over surgery * Measurable disease * No brain metastases and/or carcinomatous meningitis PATIENT CHARACTERISTICS: Age * 18 and over Performance status * Not specified Life expectancy * Not specified Hematopoietic * WBC ≥ 3,000/mm\^3 * Hemoglobin \> 10 g/dL * Platelet count \> 100,000/mm\^3 * Absolute neutrophil count ≥ 1,500/mm\^3 Hepatic * Bilirubin \< 2.0 times upper limit of normal (ULN) * AST/ALT ≤ 2.5 times ULN Renal * Creatinine \< 1.5 times ULN OR * Creatinine clearance ≥ 60 mL/min Cardiovascular * No symptomatic congestive heart failure * No unstable angina pectoris * No cardiac arrhythmia Pulmonary * No clinically active interstitial lung disease * Chronic, stable, asymptomatic radiographic changes allowed Other * No prior allergic reaction attributed to compounds of similar chemical or biological composition to study drugs or Cremophor\^® EL * No AIDS or primary immunodeficiencies * No other malignancy within the past 5 years except curatively treated squamous cell or basal cell skin cancer or carcinoma in situ of the cervix * Probability of recurrence of the prior malignancy \< 5% * No other concurrent uncontrolled illness * No ongoing or active serious infection * No psychiatric illness or situation that would preclude study compliance or giving informed consent * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * No prior chemotherapy for cancer * No other concurrent chemotherapy Endocrine therapy * Not specified Radiotherapy * No prior therapeutic radiotherapy to the head and neck region * No prior radiotherapy for cancer Surgery * See Disease Characteristics * At least 4 weeks since prior major surgery and recovered Other * No prior gefitinib or other epidermal growth factor receptor inhibitors * More than 4 weeks since prior non-approved or investigational agents * No concurrent administration of any of the following: * Phenytoin * Carbamazepine * Barbiturates * Rifampin * Hypericum perforatum (St. John's wort) * Oxcarbazepine * Rifapentine * Amifostine * Modafinil * Other CYP3A4 enzyme inducers * Other anticancer agents or investigational drugs * Combination antiretroviral therapy for HIV-positive patients

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Institutes of Health Clinical Center (CC): lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support

Bethesda, Maryland, 20892-1182, United States

Location

NCI - Metabolism Branch;MET

Bethesda, Maryland, 20892-1547, United States

Location

Related Publications (3)

• Van Waes C, Allen CT, Citrin D, Gius D, Colevas AD, Harold NA, Rudy S, Nottingham L, Muir C, Chen Z, Singh AK, Dancey J, Morris JC. Molecular and clinical responses in a pilot study of gefitinib with paclitaxel and radiation in locally advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2010 Jun 1;77(2):447-54. doi: 10.1016/j.ijrobp.2009.05.037. Epub 2009 Oct 30.

  PMID: 19879702 RESULT

• Sharp H, Morris JC, Van Waes C, Gius D, Cooley-Zgela T, Singh AK. High incidence of oral dysesthesias on a trial of gefitinib, Paclitaxel, and concurrent external beam radiation for locally advanced head and neck cancers. Am J Clin Oncol. 2008 Dec;31(6):557-60. doi: 10.1097/COC.0b013e318172d5de.

  PMID: 19060587 RESULT

• Sharp HJ, Morris JC, Van Waes C, et al.: A high incidence of oral dysesthesias unrelated to mucositis in a pilot trial of gefitinib, paclitaxel and concurrent external beam radiation in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). [Abstract] Int J Radiat Oncol Biol Phys 66 (3 Suppl 1): A-1101, S188-9, 2006.

  RESULT

MeSH Terms

Conditions

Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck

Interventions

Gefitinib; Paclitaxel; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Therapeutics

Study Officials

• Carter Van Waes, MD, PhD

  National Institute on Deafness and Other Communication Disorders (NIDCD)

  STUDY CHAIR

• John C. Morris, MD

  NCI - Metabolism Branch;MET

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: May 14, 2004
• First Posted: May 17, 2004
• Study Start: May 1, 2004
• Primary Completion: October 1, 2010
• Study Completion: November 1, 2010
• Last Updated: March 15, 2012

Record last verified: 2012-03

Locations

US (2)